Progesterone reduces hyperactivity of female and male dopamine transporter knockout mice
Progesterone reduces hyperactivity of female and male dopamine transporter knockout mice
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DOI：
10.1016/j.bbr.2010.01.015
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发表时间：
2010-05-01
影响因子：
2.7
通讯作者：
Sora, Ichiro
中科院分区：
文献类型：
--
作者：
Frye, Cheryl A.;Sora, Ichiro
精神分裂症的患病率、病程和/或预后存在性别差异。然而，可能导致女性精神分裂症患者预后更有利的神经生物学因素尚未得到很好的理解。有证据表明，类固醇激素黄体酮(P-4)可能会影响一些精神分裂症患者的情绪和/或觉醒，这让我们研究了P-4对多巴胺转运体基因敲除(DATKO)小鼠的影响，DATKO是精神分裂症的动物模型。我们的假设是，P-4在改善Datko的行为表型方面比赋形剂有更大的效果，比野生型的小鼠更有效果。实验前1h皮下注射P-4(10 mg/kg)或赋形剂，进行脉冲前抑制(PPI)、活动监测器或野外试验。与野生型小鼠相比，Datko小鼠的PPI受到了损害，但P-4没有影响。在活动监测器中，与野生型对照组相比，Datko小鼠在60分钟的测试中表现出明显更大的行走距离。在野外，与野生型小鼠相比，Datko小鼠的总条目数量明显更多，但中央条目数量更少。给予P-4可减少Datko小鼠在活动监测器和旷场的多动，但不改变野生型小鼠的运动行为。P-4增加了Datko和野生型小鼠的中央条目数量。因此，给Datko雌性或雄性小鼠注射P-4可以部分减轻它们的过度活动表型。(C)2010爱思唯尔B.V.保留所有权利。
There are gender differences in prevalence, course, and/or prognosis of schizophrenia. Yet, neurobiological factors that may account for the more favorable outcomes of women with schizophrenia are not well understood. Evidence that the steroid hormone, progesterone (P-4), may influence mood and/or arousal among some people with schizophrenia led us to examine the effects of P-4 on dopamine transporter knockout (DATKO) mice, an animal model of schizophrenia. Our hypothesis was that P-4 would have greater effects than vehicle to improve the behavioral phenotype of DATKO, more so than wildtype, mice. Young adult, male and female DATKO mice and their wildtype counterparts were subcutaneously administered P-4 (10 mg/kg) or vehicle 1 h prior to testing in pre-pulse inhibition (PPI), activity monitor, or open field. DATKO mice had impaired PPI compared to their wildtype counterparts, but there was no effect of P-4. In the activity monitor, DATKO mice showed significantly greater distance traveled during the 60 min test compared to wildtype controls. In the open field, DATKO mice made a significantly greater number of total, but fewer central, entries than did wildtype mice. Administration of P-4 decreased the hyperactivity of DATKO mice in the activity monitor and open field, but did not alter motor behavior of wildtype mice. P-4 increased the number of central entries made by DATKO and wildtype mice. Thus, P-4 administration to DATKO female or male mice partially attenuated their hyperactive phenotype. (C) 2010 Elsevier B.V. All rights reserved.